Synthesis of C5 vinyl analogues of thiolactomycin and their antitubercular properties: Olefination vs. deformylation

ORGN 49

Pilho Kim, pkim@niaid.nih.gov1, Yong-Mei Zhang2, Gautham Shenoy1, Quynh-Anh Nguyen1, Michael Goodwin1, Charles O Rock3, Cynthia S. Dowd1, and Clifton E Barry III1. (1) Tuberculosis Research Section, NIAID/National Institutes of Health, 12441 Parklawn Dr, Rockville, MD 20852, (2) Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, (3) Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105
One-third of the world's population is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), and multi-drug resistant strains of TB are spreading very quickly. Our effort to discover new compounds for TB treatment started from thiolactomycin (1: TLM). TLM has drug-like properties and is an inhibitor of bacteria cell wall biosynthesis, a proven target for TB drug therapy. Our work centers around C5 derivatization to improve the potency of TLM. Specifically, we are interested in making C5 derivatives which preserve the vinyl bond adjacent to the thiolactone ring. Synthetic approaches to the vinyl bond construction of TLM C5 derivatives (2) will be explored, focusing on various olefination conditions of aldehyde 3 that avoid deformylation. Biological activities of these compounds against Mycobacterium tuberculosis will be presented.

 

Heterocycles and Aromatics
1:00 PM-5:00 PM, Sunday, 13 March 2005 Convention Center -- Room 11A, Oral

Division of Organic Chemistry

The 229th ACS National Meeting, in San Diego, CA, March 13-17, 2005